The long-term objective of this proposal is to define the molecular events that lead to cellular transformation and the induction of the immune response to virally transformed cells using avian sarcoma viruses as a model system. Our studies have shown that BALB/c mice immunized with subtumorigenic doses of a Schmidt Ruppin avian sarcoma virus (SR-ASV) transformed cell line, SR-BALB, become resistant to subsequent challenges with tumorigenic doses of SR-BALB cells and other ASV-transformed BALB/c cell lines but not to BALB/c myeloma cells. These experiments therefore define an ASV-specific (TSTA) activity on SR-BALB cells. BALB/c mice given a single tumorigenic dose of SR-BALB cells produce high levels of antibody to the product of the ASV-sarcoma gene, pp60src, as well as to a group of nonviral proteins, designated transformation associated proteins. We have isolated a number of hybridoma cell lines which produce antibody to pp60src and others which produce antibodies to specific transformation associated proteins. The experiments proposed in this grant have three major objectives. First, we propose to use hybridoma cell lines producing antibody specific for antigenic determinants within ASV pp60src to compare the structural, biochemical and immunochemical properties of the viral src and normal cellular sarc proteins. Secondly we propose to use immune sera from tumored mice and hybridoma cell lines producing antibodies to transformation associated proteins to examine the structural, biochemical and immunochemical properties of transformation associated proteins and to define their role in the transformation process. Thirdly we propose to determine whether pp60src or any of the transformation associated proteins function as the antigen responsible for specific protection against tumor induction by SR-BALB cells, i.e., TSTA.